Abstract
The expansion of nanotechnology for drug delivery applications has raised questions regarding the safety of nanoparticles (NPs) due to their potential for interacting at molecular and cellular levels. Although polymeric NPs for drug delivery are formulated using FDA-approved polymers such as lactide- and glycolide-based polymers, their interactions with blood constituents, remain to be identified. The aim of this study was to determine the impact of size-selected Poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG) NPs on platelet activity. The NPs of 113, 321, and 585 nm sizes, were formulated and their effects at concentrations of 0–2.2 mg/mL on the activation and aggregation of platelet-rich plasma (PRP) were investigated. The results showed that NPs of 113 nm did not affect adenosine diphosphate (ADP)-induced platelet aggregation at any NP concentration studied. The NPs of 321 and 585 nm, at concentrations ≥0.25 mg/mL, reduced ADP-activated platelet aggregation. The platelet activation profile remained unchanged in the presence of investigated NPs. Confocal microscopy revealed that NPs were attached to or internalised by platelets in both resting and activated states, with no influence on platelet reactivity. The results indicate minimal risks of interference with platelet function for PLGA-PEG NPs and that these NPs can be explored as nanocarriers for targeted drug delivery to platelets.
Highlights
The past decade has witnessed a heightened interest in nanoparticles (NPs) as drug delivery systems (DDS) for the controlled and site-specific release of drugs
We previously reported the dependency of size and concentration of PLGA-PEG NPs on the aggregation profile of washed platelets (WPs) and showed a delay in the aggregation profile of WPs in the presence of NPs of 348 and 576 nm at NP concentrations of 1.5–2.2 mg/mL [9]
In the absence of NPs, platelets in platelet-rich plasma (PRP) incubated with adenosine diphosphate (ADP) at 20 μM, resulted in % PA ranging between 85.25 ± 1.18% and 87.64 ± 10.24% (n = 4–5) (Table 1)
Summary
The past decade has witnessed a heightened interest in nanoparticles (NPs) as drug delivery systems (DDS) for the controlled and site-specific release of drugs. Studies have shown the possibilities of nano-based DDS for administration through vascular pathways, such as the long-circulating Poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG)-based NPs. Recently, studies have shown the possibilities of nano-based DDS for administration through vascular pathways, such as the long-circulating Poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG)-based NPs When such nanocarriers enter the vasculature, blood components are more likely to be exposed to the bare NPs’ surfaces; this enhances their potential for interacting at both a molecular and cellular level for longer time periods [5]. Several authors have pointed out the pro-aggregatory/activation effects of some NPs on platelets, while other studies have presented their antiplatelet effects. This raises questions regarding the safety of nanomaterials, in terms of interference with haemostatic equilibrium [6,7]. We previously reported the dependency of size and concentration of PLGA-PEG NPs on the aggregation profile of washed platelets (WPs) and showed a delay in the aggregation profile of WPs in the presence of NPs of 348 and 576 nm at NP concentrations of 1.5–2.2 mg/mL [9]
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